HER2, EGFR, C-MET, VEGFR2 Expression Levels In Malignant Effusions As Potential Predictive Biomarkers For Target Therapy

Background and objective:The aim of our study was to investigate the expressed levers of HER2, EGFR, c-MET and VEGFR2 in malignant pleural and peritoneal effusions (MPPEs), and compare the protein status with primary tumors, then show directive significance for the molecular targeting therapy of effusions.Methods:MPPEs were prepared from 64 patients with the diagnosis of advanced carcinoma. Protein levels of HER2, EGFR, c-MET, VEGFR2 were evaluated by ICC on cell blocks from MPPEs, in which,25 fresh effusions were analysised by FCM. The response of these primary cancer cells, which were isolated from the MEEPs, to targeted therapeutic agents were determined by WST-8 assay. We also compared the protein expression levels of tumor cells in malignant effusions with the primary tumors.Results:HER2 by ICC was positive in 9/64(14.1%) cell blocks made from the malignant effusions. EGFRwas positive in 10/64(15.6%). c-MET was positive in 14/64(21.9%). VEGFR2 was positive in 4/64(6.25%).Concordance of HER2 and EGFR results, evaluated in primary tumors and cell blocks of malignant effusions was 94.4% (P=0.002) and 89.5%(P=0.016), respectively. The primary cancer cells isolated from effusions, which high-expression HER2, EGFR, c-MET and VEGFR2 protein, showed sensitivity to targeted therapeutic agents trastuzumab (P=0.026), cetuximab (P<0.05), crizotinib (P=0.007) and regorafenib (P=0.133) respectively, and IC50were 127?g/ml, 89.87?g/ml,5.20?g/ml,41.75?g/ml?Conclusion:The HER2 and EGFR result obtained by ICC on cell blocks concordance with primary tumors suggests that metastasis places may reflect theprotein expression of primary tumors. The concordance observed between protein status on cancer cells and the sensitivity to trastuzumab, cetuximab, crizotinib and regorafenib, which would be, to some extent, directing the clinical medication.